Identification of temperature compensation mechanisms in the mammalian circadian clock

• Project/Area Number: 15K08212
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tsuchiya Yoshiki 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30456777)
• Co-Investigator(Renkei-kenkyūsha): YAGITA Kazuhiro 京都府立医科大学, 大学院医学研究科, 教授 (90324920)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 概日リズム / 温度補償性

Outline of Final Research Achievements

In this study, we aimed to reveal mechanisms underlying temperature compensation of the mammalian circadian clock. We established a series of mouse embryonic stem cell (ESC) lines with single or multiplex clock gene ablations. ESC-based in vitro circadian clock formation assay reveals that complexed mutations, such as the CKIδ:CKIε:Cry2 mutant, exhibit an additively lengthened circadian period. By using these mutant cells, we also investigated the relation between period-length alteration and temperature compensation. Although CKIδ deficient cells slightly affected the temperature-insensitivity of period-length, we demonstrated that the temperature compensation property is largely maintained in all mutants. These results show that the ESC-based assay system could offer a more systematic and comprehensive approach to the genotype-chronotype analysis of the intracellular circadian clockwork in mammals.

Research Products

• [Journal Article] Effect of Multiple clock gene ablations on the circadian period-length and temperature compensation in mammalian cells. (2016)
  • Author(s): Tsuchiya Y., Umemura Y., Minami Y., Koike N., Hosokawa T., Hara M., Ito H., Inokawa H. & Yagita K.
  • Journal Title: Journal of Biological Rhythms Volume: 31 Issue: 1 Pages: 48-56
  • DOI: 10.1177/0748730415613888
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse. (2015)
  • Author(s): Tsuchiya Y., Minami Y., Umemura Y., Watanabe H., Ono D., Nakamura W., Takahashi T., Honma S., Kondoh G., Matsuishi T. & Yagita K.
  • Journal Title: Genes to Cells Volume: 20 Issue: 12 Pages: 992-1005
  • DOI: 10.1111/gtc.12305
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The CRISPR/Cas9-mediated disruption of clock genes in mouse ES cells. (2015)
  • Author(s): 土谷佳樹
  • Organizer: 第22回日本時間生物学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-21